Androgen Effects in HIV-infected Women

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ClinicalTrials.gov Identifier: NCT00095212

Recruitment Status
:
Completed

First Posted
: November 2, 2004

Results First Posted
: March 15, 2010

Last Update Posted
: April 14, 2010

Sponsor:

Massachusetts General Hospital

Collaborator:

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Androgen deficiency in HIV-infected women is associated with sarcopenia and may cause critical reductions in physical functioning and reduced bone density. The effects of long-term androgen therapy on lean body mass, bone density and other clinical endpoints including quality of life, functional status and neurocognitive function in HIV-infected women are not known.

Condition or disease

Intervention/treatment

HIV Infection

Drug: 1 Transdermal Testosterone (Patch)Drug: 2 Placebo Patch

Detailed Description:

We will perform an 18-month randomized, double-blinded, placebo-controlled study among relatively androgen deficient women with HIV, to determine the effects of testosterone administration on lean body mass. The administered dose will be 300 micrograms twice a week vs. identical placebo in the form of a transdermal preparation. Secondary endpoints include effects on bone density, quality of life, neurocognitive function and menstrual function. Open label administration at 300 micrograms twice a week will be initiated for 12 months in all subjects following the randomized portion of the study. Assuming a 15% dropout rate and 25 randomized patients, the probability is 80 percent that the study will detect a treatment difference at a two sided 5.000 percent significance level, if the true difference between the treatments is 2.7 kg. This is based on the assumption that the standard deviation of the response variable, lean body mass by DEXA, is 2.3 kg, as was shown by Choi et al1 over 12 weeks in HIV-infected women at the same dose of 300 ug 2x/week.

Represents change in the mean score from baseline to 18 months. Depression was evaluated with the Beck's Depression Inventory (BDI). The BDI is a 21-item self-report instrument used to assess the presence and severity of symptoms of depression. A Total score in the range of 0-13 is considered minimal, 14-19 is mild, 20-28 is moderate, and 29-63 is severe.

Safety: Number of Subjects Reporting a Skin Reaction to the Patch [ Time Frame: Baseline (time 0) to 18 months ]

Represents number of subjects who reported this symptom from baseline to 18 months. Every 6 weeks,subjects were counseled on appropriate barrier contraception methods and a urine pregnancy was performed. Subjects who experienced increased hair growth (facial hair) could remain in the study on a lower dose of testosterone (1 patch per week), but dose reductions were not necessary and full dosing was continued throughout the study for all subjects. Changes in menstrual status, missed periods and/or irregular bleeding, were noted and reported back to the primary care physician if significant.

Represents number of subjects who reported this symptom from baseline to 18 months. Every 6 weeks,subjects were counseled on appropriate barrier contraception methods and a urine pregnancy was performed. Subjects who experienced increased hair growth (facial hair) could remain in the study on a lower dose of testosterone (1 patch per week), but dose reductions were not necessary and full dosing was continued throughout the study for all subjects. Changes in menstrual status, missed periods and/or irregular bleeding, were noted and reported back to the primary care physician if significant.

Represents number of subjects who reported this symptom from baseline to 18 months. Every 6 weeks,subjects were counseled on appropriate barrier contraception methods and a urine pregnancy was performed. Subjects who experienced increased hair growth (facial hair) could remain in the study on a lower dose of testosterone (1 patch per week), but dose reductions were not necessary and full dosing was continued throughout the study for all subjects. Changes in menstrual status, missed periods and/or irregular bleeding, were noted and reported back to the primary care physician if significant.

Safety: Number of Subjects Reporting a Change in Menstrual Status (Reported More Than One Period in 1 Month or Missed a Period During a Monthly Cycle) [ Time Frame: Baseline (time 0) to 18 months ]

Represents number of subjects who reported this symptom from baseline to 18 months. Every 6 weeks,subjects were counseled on appropriate barrier contraception methods and a urine pregnancy was performed. Subjects who experienced increased hair growth (facial hair) could remain in the study on a lower dose of testosterone (1 patch per week), but dose reductions were not necessary and full dosing was continued throughout the study for all subjects. Changes in menstrual status, missed periods and/or irregular bleeding, were noted and reported back to the primary care physician if significant.

This test assesses verbal learning and memory. Subjects are given a list of 12 words and asked to repeat as many words as they can recall during 3 separate trials. The Total Recall Z score is calculated based on the sum of total correct responses for Trials 1,2,& 3. A Z score of 0 equals the 50 percentile, a Z score of 1 is 1 standard deviation above the mean and a Z score of -1 is 1 standard deviation below the mean. The lowest and highest T scores for the HVLT-R are ≤20 and ≥80. This correlates to lowest and highest Z scores of ≤ -3.0 and ≥3.0. A lower Z score is indicative of poor recall.

Represents change in isometric force (measured in kilograms) from baseline to 18 months. Peak isometric force of total knee flexion and extension were measured on the best of 2 repetitions for which subjects held a maximum contraction for 5 seconds.

Represents change in isometric force (measured in kilograms) from baseline to 18 months. Peak isometric force of total knee flexion and extension were measured on the best of 2 repetitions for which subjects held a maximum contraction for 5 seconds.

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Ages Eligible for Study:

18 Years to 55 Years (Adult)

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Female 18 - 55

BMI less than or equal to 26

HIV-infected

Androgen deficient, with free testosterone < 3 pg/mL

Stable antiretroviral regimen for 3 months prior to study

Tubal ligation, hysterectomy, or verbalized understanding of appropriate barrier contraception methods. Subjects will be counseled in appropriate barrier contraception methods and the counseling will be documented.

Exclusion Criteria:

Use of anabolic agent, including testosterone, GH or other preparations within 3 months of the study.

Use of megestrol acetate within 3 months of the study

Use of estrogen or any preparation known to affect bone density or bone turnover.This includes oral contraceptives, depo provera or combined progesterone-estrogen injections, and transdermal contraceptive patches.

Pregnant or breast-feeding

Hgb < 9.0 mg/dL

Current participation in another research study conducted by this investigator or past participation in the DHEA study funded by the same grant as this protocol.